PB1957: CIRCULATING MIRNA-16 AND MIRNA -21 EXPRESSION LEVELS IN MYELOMA; PRELIMINARY RESULTS.
Authors: A.-I. Gkioka, M. Tsota, M. Papadatou, A. Gkiokas, A. Alexandropoulos, V. Bartzi, G. V. Dedousis, M.-C. Kyrtsonis
Journal: HemaSphere (2022)

Background: MicroRNAs (miRNAs) are short, noncoding RNAs of 19–22 nucleotides that participate in gene expression regulation. Many studies have focused on circulating miRNAs which might be potential biomarkers. In Multiple Myeloma (MM) they are involved in bone marrow microenvironment, methylation, immune regulation, genomic instability, and drug resistance. Their exact role has not been fully explored yet. Aims: We investigated hsa-miR-16-5p miRNA-16 and miRNA-21 expression levels in MM patients’ serum, their possible prognostic role and correlations with disease parameters. Methods: Thirty-seven MM patients were studied, of whom 22 were at diagnosis and then all 37 at relapse before lenalidomide-dexamethasone treatment (RD). We analyzed miRNA-16 and -21 expression in serum of 49% were women and 51% men with median age 69 yrs (range 49-84), 46% were ISS 1, 19% ISS 2 and 35% ISS 3. Ig type was IgG in 62%, IgA in25%, Light-Chain in 11% and other in 2%. Median OS was 75 mo. Clinical characteristics and laboratory tests, as well as sera samples, at diagnosis and before RD treatment were collected after patients’ informed consent. Frozen sera from patients and 14 healthy individuals (HI) were used for miRNA detection processed by Real–Time PCR. MiRNA expression was compared to exogenous has-miRNA-39-5p. Two-Fold change (x2) expression (upregulation) of miRNA was considered as overexpression. Statistical analysis was performed with the SPSS v.25 software. We analyzed thereafter the compared levels of miRNA-16 -21 termed as hsa-miR-16 and hsa-miR-21. Upregulation by one fold was used as cutoff value for survival analysis plotted by Kaplan Mayer. Results: Median hsa-miR-16 expression at diagnosis was 0.23 and 0.64 at relapse. Median hsa-miR-21 expression was 0.63 at diagnosis and 1 at relapse. In HI, median expression levels were 13.8 for hsa-miR-16 and 13.3 for hsa-miR-21. The difference between HI and patients was significant, with regard to hsa-miR-16 at diagnosis (p= 0.003) and at relapse (p=0.007), as well as to hsa-miR-21 at diagnosis (p=0.041) and relapse (p=0.001). A correlation between hsa-miR-16 and hsa-miR-21 was found at diagnosis (p=0.0003, r=0.706) and before RD initiation (p =0.02, r= 0.438). Hsa-miR-16 at diagnosis correlated with abnormal Calcium (p=0.05, r=-0.424), Creatinin (p=0.01, r=-0.534), while hsa-miR-21 expression levels at diagnosis were negatively correlated with abnormal Creatinin (p=0.04, r=0.438). No correlation was observed between miRNA serum levels and age and sex at diagnosis and at RD initiation. Hsa-miR-21 before RD treatment correlated with median bone marrow infiltration (r=0.549, p=0.02), RISS (r=0.769, p=0.005) and the type of relapse to lenalidomide (clinical or biochemical) (r= -617, p=0,02), while hsa-miR-16 correlated with abnormal LDH (r = 0.365, p=0.03), number of previous treatment lines (r=- 0.334, p=0.04) and negatively with creatinin (r= - 0.427, p=0.01). Decreased has-miR-16 expression at diagnosis was related to better survival (p=0.16). Summary/Conclusion: We observed correlations between factors of MM disease activity and hsa-miR-16 and hsa-miR-21 while in addition hsa-miR-16 expression levels predicted survival. Larger studies shall confirm these results. First Authors; Gkioka A-I *, Tsota M*, *equal contribution, Signing Authors; Kyrtsonis MC§, Dedousis VG§ §equal contribution